Project Summary Recent progress in the Center for Biomedical OCT Research and Translation has resulted in 1) the ability to detect and map polarimetric signatures for tissue characterization, and 2) fast and effective methods for quantitative angiographic imaging with microscopic resolution over fields of view as large as 10?s of cubic centimeters. Motivated by recent insights from autopsy and clinical studies of Alzheimer?s disease patients, we seek to extend our polarimetry and angiography capabilities to retinal sensing in order to enable new breakthroughs in noninvasive biomarkers for detecting and monitoring this disease. Specifically, we will extend our methods for precise, rapid, and robust polarimetric and quantitative angiographic retinal optical coherence tomography and will demonstrate feasibility and reproducibility of these methods in human volunteers. At the conclusion of this work, we will have a clinical imaging system suitable for integration into ongoing clinical research under the direction of Dr. Peter Snyder, a leading Alzheimer?s disease investigator. Relevance Recent studies suggest that almost 40 percent of US adults 50 and older are at risk for the development of Alzheimer?s disease. Even though it is unclear how many of these patients will develop dementia, the potential implications are staggering. While ongoing research aims to identify new therapeutic strategies to reduce risk or diminish progression, there is a clear need for novel techniques that could be widely deployed for objective clinical diagnosis and assessment. The proposed methods are noninvasive and could potentially be rapidly integrated into an existing infrastructure of ophthalmic instrumentation to meet this need.